Cloning and Analysis of Head Tilt, A Vestibular Mutant

描述(申请人提供)：复杂生物体感知的能力 重力、运动和空间方向是由 前庭系统。拟议中的研究将探讨 一种突变的小鼠头倾斜(HET)，这已经扰乱了重力感受器功能。 在初步研究中，这种突变的病理学揭示了一种完整的 没有耳石，碳酸钙晶体刺激 直线加速和重力作用下的前庭斑点。这样做的目的是 应用程序简单明了，重点突出。我们打算分析het突变体 并克隆het基因，以了解其功能。 耳石发育。拟议的研究旨在：1)完成物理地图 Het关键区，并鉴定和鉴定het基因；2)进一步 用组织学、电子显微镜和组织学方法鉴定het突变表型 胚胎干细胞(ES)方法；以及3)分析耳锥维持 条件性基因表达技术。这些实验加在一起将 提供对前庭功能和疾病的更清晰的了解。

DESCRIPTION (provided by applicant): The ability of complex organisms to sense gravity, motion, and spatial orientation is a crucial function enabled by the vestibular system. The proposed studies will investigate the molecular basis of a mouse mutation head tilt (het), which has disrupted gravity receptor function. In preliminary studies, the pathology of this mutant has revealed a complete absence of otoconia, the calcium carbonate crystals that stimulate the vestibular maculae during linear acceleration and gravity. The goals of this application are straightforward and focused. We intend to analyze the het mutant phenotype and to clone the het gene in order to understand its function in otolith development. The proposed studies aim to: 1) complete a physical map of the het-critical region and identify and characterize the het gene; 2) further characterize the het mutant phenotype by histological, electron microscopic, and embryonic stem (ES) cell approaches; and 3) analyze otoconial maintenance using conditional gene expression technologies. Together these experiments will provide a clearer understanding of vestibular function and disease.